P1118: LONGER FOLLOW-UP FROM THE PIVOTAL EPCORE NHL-1 TRIAL REAFFIRMS SUBCUTANEOUS EPCORITAMAB INDUCES DEEP, DURABLE COMPLETE REMISSIONS IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA
Authors: Wojciech Jurczak, Herve Ghesquieres, Yasmin Karimi, Chan Cheah, Michael Roost Clausen, David Cunningham, Young Rok Do, David Lewis, Robin Gasiorowski, Tae Min Kim, Marjolein Van Der Poel, Michelle Limei Poon, Tatyana Feldman, Kim Linton, Anna Sureda, Martin Hutchings, Salim Kanoun, Laetitia Vercellino, Mariana Cota Stirner, Stephanie Mcgoldrick, Yan Liu, Mariana Sacchi, Pieternella Lugtenburg, Catherine Thieblemont
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Outcomes are poor for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Effective treatments that drive deep, durable responses and long-term benefit are needed. In the pivotal EPCORE™ NHL-1 trial (NCT03625037), single-agent epcoritamab showed high complete response (CR) and MRD-negativity rates and a manageable safety profile as an off-the-shelf, subcutaneous, CD3xCD20 T-cell–engaging bispecific antibody (Thieblemont et al, JCO 2022). Aims: To present updated results from the EPCORE NHL-1 LBCL expansion cohort, including longer follow-up, in a challenging-to-treat population. Methods: Patients with R/R CD20+ LBCL received subcutaneous epcoritamab (step-up priming and intermediate doses followed by 48-mg full doses) in 28-d cycles: QW, cycles 1–3; Q2W, cycles 4–9; Q4W, cycles ≥10 until PD or unacceptable toxicity. Informed consent was obtained. Results: As of November 18, 2022, of 157 patients (median age, 64 y) with LBCL (including DLBCL [n=139; 12/88 double/triple-hit by FISH], HGBCL [n=9], PMBCL [n=4], and FL grade 3B [n=5]), 36 remain on treatment. Patients had a median of 1.6 y from initial diagnosis to first dose and a median of 3 (range, 2–11) prior lines of treatment; 61% of patients had primary refractory disease, and 39% had prior CAR T, of whom 75% progressed within 6 mo of treatment. Median follow-up was 20 mo (range, 0.3+ to 28.2). Patients received a mean of 9.1 cycles. LBCL overall response and CR rates were 63.1% and 39.5%, respectively, and were consistent for DLBCL (61.9% and 39.6%). Median duration of CR was 20.8 mo. Median time to CR was 2.7 mo; 8 patients converted from partial response to CR at ≥36 wk. Median overall survival was 18.5 mo (95% CI, 11.7–not reached [NR]) for patients with LBCL and 19.4 mo (95% CI, 11.7–NR) for patients with DLBCL (Figure). Median overall survival was NR (95% CI, NR–NR) in patients who achieved CR; at 9, 12, and 15 mo, an estimated 98.3%, 95.0%, and 88.3% of complete responders were alive, respectively. Additionally, median duration of response among patients with CR was 20.8 mo (95% CI, 17.3–NR), and an estimated 91.2%, 85.2%, and 79.0% of complete responders remained in response at 9, 12, and 15 mo, respectively. Median progression-free survival was NR (95% CI, 18.5–NR) among complete responders; an estimated 91.1%, 87.2%, and 81.3% of complete responders remained progression free at 9, 12, and 15 mo, respectively. The most common treatment-emergent adverse events of any grade (G) were CRS (51%), neutropenia (24%), pyrexia (24%), fatigue (23%), nausea (22%), and diarrhea (21%). Nine patients (6%) had G1–2 ICANS, and 1 patient had a G5 event with confounding factors. Fatal treatment-emergent adverse events occurred in 15 patients; 2 were considered related (COVID-19, ICANS). CRS was predominantly low grade (48% G1–2; 3% G3) and occurred following the first full dose (cycle 1, day 15). One patient discontinued treatment due to G1 CRS. Summary/Conclusion: These data with longer follow-up reaffirm single-agent subcutaneous epcoritamab induces durable CRs with improved outcomes and a manageable safety profile for patients with R/R LBCL. No new safety signals were observed in these hard-to-treat patients. These impressive data support the ongoing phase 3 studies evaluating epcoritamab across different lines of treatment and in various combinations.Keywords: Bispecific, Non-Hodgkin’s lymphoma, Hematological malignancy